The overall goal of this proposal is to develop, evaluate, and utilize x- ray CT derived indicator dilution curves to quantitate the physiologic supply side of myocardial function in terms of the three-dimensional distribution of intramyocardial blood volume, perfusion, and permeability- surface area product. Each of five goal addresses one aspect of myocardial perfusion by means of a sequential development, evaluation and application phase. Much of the development of the basic image analysis techniques has already been accomplished, either by ourselves or by other investigators, hence this proposal addresses primarily development of mathematical models needed to compute the physiological parameters. In this proposal we will use the Dynamic Spatial Reconstructor (DSR), a volume imaging, fast CT scanner, to study experimental animals and radiologic phantoms. In AIM I we propose to show that the CT indicator dilution curves correspond directly to the indices of solute transport estimated using traditional, more invasive, methods. In AIM II we propose to show that intramyocardial blood volume, estimated by fast CT, can be used to test hypotheses as to the relative importance of microvascular recruitment, and the relationship of capillary permeability- surface area product to flow. In AIM III CT estimates of myocardial perfusion will be used to quantitate the functional significance of a coronary stenosis and the myocardial volume at risk of infarction. In AIM IV a method for quantitating permeability-surface area product will be developed and used in assessing the effects of myocardial ischemia and edema. In AIM V the transfer function of the myocardial vascular bed will be used to enable replacement of aortic root injections with central venous injections. The significance of this work is that these studies should go a long way towards developing a technique that is needed to answer important clinical questions about the functional significance of a coronary artery stenosis and important physiological questions about the relationship between myocardial flow and solute transfer. These same techniques should be almost directly applicable to other organs. As the DSR scanner's 3D images can be mathematically reprojected, we can also use these 3D image data to demonstrate the limits of the validity of these techniques (developed for 3D) in the more widely accessible 2D angiographic data. These developments will, most likely, be almost directly applicable to other fast CT (e.g., Imatron) and in part to radionuclide emission and MRI images.